While there is general agreement regarding the principles of antimicrobial therapy, the implementation of these principles is often difficult in practice. Nonetheless, they provide a basis that allow for the clinician to optimize outcomes in patients suffering from infectious diseases. In general, the use of antimicrobials can be considered either Prophylactic, Preemptive, Empiric or Definitive antibiotics are used Prophylactically to prevent infection, Preemptively to abort infection, Empirically to provide initial control of infection in the absence of knowledge of its etiology and Definitively to cure infection of known etiology. Examples of prophylactic antibiotic use in the outpatient setting include the prevention of endocarditis and selected patients undergoing high-risk dental procedures. In the inpatient setting, antibiotic prophylaxis to prevent postoperative surgical infections is another important example. Perhaps the commonest use of preemptive therapy occurs in Immunosuppressed transplant recipients, to prevent the development of end organ infection in patients with Cytomegalovirus circulating in their blood. Although preemptive therapy is sometimes practiced in the realm of fungal infections, there are no good examples in dealing with bacterial infections. In the outpatient setting, common uses of empiric therapy, including in dealing with patients with acute sinusitis, community acquired pneumonia and cystitis. In the first two of these, the clinician seldom knows the precise etiology of the infection including whether it is actually caused by bacteria. Antibiotic administration is empiric in the initial management of urinary tract infections but may require alteration depending on the results of urine culture and susceptibility, at which time, definitive therapy may be administered. In the inpatient setting, the use of empiric antibiotic therapy is widespread and includes patients with community and hospital-acquired pneumonia, fever with neutral pneumonia, undifferentiated sepsis and others. Finally, definitive or targeted antibiotic therapy is tailored to treat infection in which the etiologic pathogen and it's antimicrobial susceptibility pattern are known. We will now focus on empiric therapy, more specifically on empiric therapy and sepsis. The importance of the choice of an appropriate empiric antibiotic regimen and patients with severe infection is evidenced by the fact that inappropriate therapy defined as the absence of an administered antibiotic to which the subsequently identified pathogen is susceptible, is associated with increased mortality. Furthermore, the antibiotic must be administered as rapidly as possible, preferably within one hour. In patients with septic shock, there is an almost eight percent increase in mortality, for every hour in delay in initiation of appropriate antibiotic therapy beyond that first hour. Other important elements in the choice of antibiotics for empiric use include the site of infection and the likelihood of antibiotic resistance. Furthermore, identifying the presumptive site of infection provides clues regarding the likely pathogens and may also allow for the possibility of source control, such as drainage of an abscess or removal of a central venous access device. Clearly, the likely pathogens in each case are different and suspected, eurosepsis they're likely to be gram-negative rods, whereas in ammonia other pathogens are likely. The clinician should also assess the likelihood that the pathogen causing the infection is resistant to many commonly used antibiotics. Elements which might lead one to that suspicion include a history of recent antibiotic exposure, known colonization with antibiotic resistant pathogens, frequent exposure to healthcare facilities, and knowledge of local antibiotic resistance patterns. Also to be taken into account are host factors. Some of these for instance might preclude the use of individual antibiotics, for example, the presence of life-threatening allergies to a particular antibiotic or class of antibiotics. Also, factors that might steer one away from certain antibiotics may include an increased risk of related toxicity. Examples include the use of Nephrotoxic agents such as Aminoglycosides or Amphotericin in patients or already have marginal or unstable renal function and especially, if they are receiving other nephrotoxic drugs. Of critical importance in the decision-making process is an assessment of the severity and trajectory of the illness. How sick is the patient and how rapidly are they likely to deteriorate? What in fact is the margin for error? If I give the wrong antibiotics today, will the patient still be alive tomorrow? This sort of assessment dictates a lot of the kind of decisions that are made in the management of the patient. Other recommendations include ignoring colonization and only treating infection, obtaining cultures before the initiation of antibiotic therapy without causing inordinate delay in the institution of antibiotic administration and others. Having initiated empiric therapy, the clinicians job is nowhere near completed. The choice of therapy should continually be reevaluated. This approach is supported by a variety of published recommendations thus the surviving sepsis campaign recommendation state that, in patients with severe septic shock or severe sepsis without shock, the administration of effective intravenous antimicrobials within the first hour of recognition should be a goal of therapy. But they also state that the antimicrobial regimen should be a reassessed daily for potential de-escalation, to prevent the development of resistance, to reduce toxicity and to reduce costs. De-escalation however, is not the only decision that might be made, in fact for example, therapeutic escalation may be warranted in some cases. An important reassessment checkpoint generally arises at 48 to 72 hours, at which time much microbiological information is available, as his clinical information indicating the evolution of the patient's clinical status. At this point, a formal antibiotic timeout should be taken and documented. The decisions during the timeout must take into account the information mentioned above in the context of the bug, the drug, and the host. If a pathogen is identified and it's antimicrobial susceptibility pattern has been determined or is highly suspected, and adjustment in antibiotic choice may be indicated, as in the case of a bug drug mismatch. If cultures are negative decision-making is often more complex, it must be made an assessment of the patient's clinical status and trajectory. There are three general possibilities with regard to clinical status. There could have been no improvement, the patient could be improved or in fact, the patient's clinical status may have worsened. Let's take the case in which the patient is improving. In this instance, the clinician may either continue the therapy, modify it or in fact discontinue it depending on clinical status and other available information such as serum procalcitonin measurements. If a pathogen has been identified, any bug drug mismatch present should be resolved despite the improvement, redundancies and coverage addressed, an antibiotic spectrum narrowed. Adverse effects of antibiotic use dealt with, dosing issues examined and anticipated duration of therapy addressed. Dosing should be optimized and consideration given to IV to oral conversion may be anticipated. The issue of the appropriate duration of antimicrobial therapy is sometimes unclear, but in some instances, at least national guidelines provide clear recommendation. Thus it is recommended that hospital-acquired pneumonia be treated for only seven days. Recent data suggests that in cases in which daily ventilatory settings are minimal, that is a peep of five millimeters of mercury or less and Fio2 of 0.4 or less, antibiotics may be discontinued after three days. An 80% decrease in serum procalcitonin or reaching a normal value, may also allow early discontinuation of antibiotic therapy. The clinical pulmonary infections score is also been used to discontinue antibiotics at three days, but its usefulness has recently been questioned. Decision-making regarding starting and stopping antibiotic therapy is more often than not fraught with ambiguity because of inadequate data. As William Osler said, "Medicine is a science of uncertainty and an art of probability." We can nonetheless optimize our approach by utilizing the principles of antibiotic therapy..
